Several key areas related to the understanding of immune regulation will be studied using in-vitro or co-culture of autologous T and B cells and radioimmunoassay of IgG and IgM production after 7 days of culture. Relative contributions of radiosensitive suppressor T cells will be estimated using assays before and after 2000 rads irradiation of T cells isolated by neuraminidase rosetting. In addition attempts will be made to study the effects of soluble suppressor factors elaborated by cultured T or B cells using co-culture of cells separated by membranes. The effect of thymic hormone preparations (TP5) will be studied using this in vitro system. Autologous as well as allogeneic cellular interactions will be examined using lymphocytes from human cord bloods, patients with acquired immune deficiency, rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue diseases. Cellular interactions will also be examined in a group of patients with chronic active liver disease with the aim of dissecting out identifiable defects in cell to cell cooperation. Attempts will be made to produce heterologous reagents capable of detecting unique determinants on human suppressor cells using immunizations with T cells from patients with immune deficiency demonstrated to show in vitro suppressor T cell activity. Reagents capable of reliable identification of functional suppressor T cells will be utilized for enumeration and identification of such mononuclear cells in tissue lesions of patients with connective tissue as well as liver disease. Broad analysis of the functional importance of human Ia-like antigens will involve ELISA assays and characterization of human Ia-like antigens in serum during disease. An attempt will also be made to produce disease-related anti-Ia antisera using immunization of rabbits with serum pools from patients with restricted patterns of Dw type. Finally, analysis of tissue receptors for immune complexes will be made using primate eyes, human choroid plexus and cardiac tissues from patients with acute rheumatic fever. The relationship between quantitative and qualitative aspects of circulating immune complexes and skin as well as renal toxicity to gold compounds will be studied in rheumatoid arthritis.